trends in synthetic biology 2011

The 2010 has been the year of Venter's synthetic genome. What about 2011, new developments at the horizon?

Synthetic physiology. One goal of synthetic physiology would be to integrate a new genetic function into mammalian cells, i.e., a circuit that can detect a diseased state and then trigger a therapeutic appropriate response. Two studies are pursuing this goal. The group of Martin Fussenegger (Basel, Switzerland) reported their success in developing a light-driven mechanism to control transcription. The 'photoactivation' switch uses melanopsin, a retinal protein that release a calcium surge when exposed to blue light. The researchers engineered it so that the transient of calcium would activate, via calcineurin, the transcription factor NFAT. To prove that the technique has therapeutic potential, they coupled NFAT activation to insulin production in a mouse model of diabetes. When bathing in blue light, the diabetic mice 'switched on' insulin production and prevented the dangerous glycemic excursion consecutive of eating glucose. [Science 332, 1565-1568; 2011]. Interestingly, the trigger of synthetic circuits could be also an endogenous one: the groups of Weiss (Cambridge, MA) and Benenson (Basel, CH) developed together a miRNA-based synthetic logic circuit that identifies and specifically kills HeLa cancer cells. The genetic circuit senses the expression level of a customizable set of endogenous miRNAs and after customizable AND or NOT gating, triggers a customizable cellular response (i.e., apoptosis), opening the way to the design of synthetic circuits for futuristic clinical purposes. [Science 333, 1307-1311; 2011]

Synthetic life? Venter's cells were not completely synthetic as only the DNA was artificially made. But, is it possible to build a fully synthetic cell? Some progress come from an unexpected approach: synthetic inorganic life. Despite the strong claims of bacteria substituting phosphorous with arsenic in their DNA have been largely criticized, the research of inorganic life continues on different fronts: for instance, the group of Lee Cronin (University of Glasgow) is trying to create self-replicating, evolving, inorganic cells that would essentially be 'alive'. Simple inorganic chemical cells (iCHELLs) can be obtained at the liquid-liquid interface between aqueous solutions of POM (polyoxometalate) clusters and coordination-complex cations with the aid of very simple instrumentation. The researchers placed a drop of cation solution on a glass coverslip and POM solutions were then injected into the droplet using Eppendorf femtotips. The process can be nested resulting in compartmentalization of internal membranes that were found to control the passage of materials and energy, meaning that several chemical processes can be isolated within the same iChell, just like biological cells [Angewandte Chemie Int Ed, 50(44); 10373-76; 2011]. Future steps under investigation are the engineering of iCHELLS able to undergo fission into daughter iCHELLs, just like inorganic life. For the moment, a second in vitro study lead by Laura Martini and Sheref Mansy shows that cell-like systems with riboswitches can be used to control protein expression under fully defined conditions in water-in-oil emulsions [Chem Commun 47; 10734-36; 2011].